Proteins
Biol 135 Lecture:
IV. Structure, Function and Source of Macronutrients.
C. Proteins
Proteins are the most versatile and ubiquitous of the organic molecules in the human body. They
are an integral part the body and are found throughout the structures and systems of the human
body. At least 10,000 different proteins help to make up what you are. Like all other organic
molecules that we ingest, proteins are crucial for normal growth and development of the body,
especially critical for muscle and bones. They are literally everywhere, making up the ‘plasma
proteins’ of the blood; they also form a major component of the plasma membrane of all cells;
they function as receptors, transporters and enzymes. Proteins are also found in muscle, bone,
skin, hair, and virtually every other body tissue. All the enzymes that catalyze the thousands of
chemical reactions in the body are proteins! The very molecule that carries 98% of the oxygen
(O2) from your lungs to you tissues is the protein molecule hemoglobin. With such varied and
prominent functions, there can be a high turn-over of protein in the body, so it becomes very
important to ensure adequate supply in your diet to match your needs.
Amino Acids Make Proteins
Proteins are made from building blocks (or subunits) called amino acids. Our bodies make
amino acids in two different ways: Either from scratch, or by modifying others. Some amino
acids are called essential amino acids, because they must come from the food we eat in our
diets. Animal sources of protein tend to deliver all the amino acids we need. Other protein
sources, such as fruits, vegetables, grains, nuts and seeds, lack one or more essential amino acids.
Figure 1. Show the “Generalized Amino Acid” structure. Each of the 20 amino acid has a central Carbon
(C) that is flanked on one side by an amino group (NH2) and on the other side by a carboxylic acid
group (COOH). The central C as a H atom attached to is and lastly, is the R group which represents the
“Variable” or “Functional” side group. It is R portion that makes each amino acid unique. The number
and sequence of amino acids in each protein determines its unique shape and function.
Of the proteins that are made from the 20 different amino acids, 9 are essential, meaning
humans cannot make them, but must eat them in their diets. The remaining 11 are not essential,
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as we can synthesize them in our bodies. The variable (R) group is this is the only part of the 20
amino acids in human nutrition that is different and unique to each.
This side group (R) can be basic, acidic, polar, non-polar, charged, or neutral. The way this
side group interacts with other side groups in the peptide chain will have an impact on its three
dimensional (3D) shape. In the protein world, shape equals function, so the shape a protein takes
is crucial to how that protein operates. If a protein loses its shape due to some type of stress (e.g.,
heat, change in pH, etc.) it can become denatured (change its shape) and loose its normal
function (see later in this section).
The 20 Amino Acids: Building Proteins from Amino Acids
As mentioned, for humans, an essential amino acid or indispensable amino acid is an amino
acid that cannot be synthesized de novo by humans and therefore must be supplied in our diet.
The nine (9) essential amino acids for humans are:
Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and
Valine.
There are six (6) amino acids are considered conditionally essential in the human diet, meaning
their synthesis can be limited under special pathophysiological conditions. These are:
Arginine, Cysteine, Glycine, Glutamine, Proline and Tyrosine.
There are five (5) amino acids are dispensable in humans, meaning they can be synthesized in
the body. These five are:
Alanine, Aspartic Acid, Asparagine, Glutamic Acid and Serine.
Essential Amino Acids in Humans
Essential
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine
Nonessential
Alanine
Arginine
Asparagine
Aspartic acid
Cysteine
Glutamic acid
Glutamine
Glycine
Proline
Serine
Tyrosine
Figure 2. The building of peptides, oligopeptides and proteins is done by using the amino acids listed in
the table above. As shown in the diagram to the right, adding amino acids together in a linear sequence,
the amino end always combines with the carboxylic end when making a covalent peptide bond. Two
amino acids combine in a dehydration synthesis reaction to create a dipeptide.
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Can you Remember all of the Essential and Non- Essential Amino Acids?
It may seem like a tall order at first, to remember 20 amino acids when you may not have even
known one of their names prior to reading the list presented in Figure 2. A good way to
remember anything that seems complicated at first is to see if there is a pattern you can create
and use to help you remember things.
Often a mnemonic device or saying is a good tool that can be used to remember a long series of
items or words. It is done by creating a saying that is easy to remember, typically by using the
first letter of each word or structure in the series – then you substitute the ‘real words’ into the
saying. Because the mnemonic saying easily triggers the pattern for the more complicated or less
familiar set of terms, it can be very handy!
Here is a simple mnemonic for remembering the essential amino acids: PVT TIM H*LL. It can
be read as “Private Tim Hall”, knowing that the nine capital letters in this saying represent the
first letters of the nine essential amino acids.
P.V.T.
 P = Phenylalanine
 V = Valine
 T = Threonine
T.I.M.
 T = Tryptophan
 I = Isoleucine
 M = Methionine
H.L.L.
 H = Histidine
 L = Leucine
 L = Lysine
For the remaining 11 non-essential amino acids, there is sort of an easy way to put the capital
letters that represent the amino acids in a memorable pattern:



AAAA
CGGG
PST
Four A’s, one C, then three G’s, then like “pst, over here” at the end.
Alanine
Arginine
Aspartic acid
Asparagine
Cysteine
Glutamic acid
Glutamine
Glycine
Proline
Serine
Tyrosine
Task: See if you can list all of the 20 amino acids in human nutrition, and differentiate
between the 9 essential and 11 non-essential. The best way to do this is to write out the names
fully – several times! *Note: You create and maintain at least 26 neural pathways every time you
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write by hand. You may have never even heard of an amino acid before now, but here they are
and if you write out the 2 lists several times on a blank piece of paper, referring to the notes and
using the mnemonics as a trigger, you will be surprised at how you can memorize these names.
A little later, take a blank piece of paper and see how many you can write without looking at the
notes. Practice until you can write them all out, and after that, it will be hard to forget!
Amino Acid Key for Figure Below
Essential
Nonessential
Histidine (His)
Alanine (Ala)
Isoleucine (Ile)
Arginine (Arg)
Leucine (Leu)
Asparagine (Asn)
Lysine (Lys)
Aspartic acid (Asp)
Methionine (Met)
Cysteine (Cys)
Phenylalanine (Phe) Glutamic acid (Glu)
Threonine (Thr)
Glutamine (Gln)
Tryptophan (Trp)
Glycine (Gly)
Valine (Val)
Proline (Pro)
Serine (Ser)
Tyrosine (Tyr)
Figure 3. The 20 amino acids in 3 letter code, colors: Blue = amine; pink = acid; red = variable groups.
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Figure 4. Like ‘peals on a string’, the amino acids line up and form a peptide or protein of a unique
length and sequence. The Primary Structure of a protein is the linear sequence of amino acids and is
critical for determining how the entire structure will fold and behave.
The linear sequence of amino acids is very important - A great example of this significance is
seen in the disease of sickle cell anemia. Sickle cell anemia gets its name from the abnormal
shape of red blood cells in affected individuals, the red blood cells tend to collapse and give the
cells an abnormal crescent shape, like a sickle appearance. This is in contrast to the normal biconcave disc appearance of these cells. Due to a change in one amino acid in a chain of 126,
these sickle shaped red blood cells are very fragile and the result is severe anemia from a
decreased number of red blood cells. The abnormally shaped red blood cells in this disease also
cause the blockage of blood vessels and other painful symptoms in patients.
Figure 5. The substitution of the 6th amino acid in the β-globin chain subunit of hemoglobin (Hb), from
glutamic acid to valine, gives rise to changes in the shape and function of note only the Hb molecule, but
also the entire red blood cell (erythrocyte). The result is ‘sickle cell anemia’ which impairs blood flow
and oxygen delivery to tissues.
The abnormal shape of the cells in individuals with sickle cell anemia comes from a defective
protein within the blood cells themselves. This defective protein is hemoglobin.
The normal hemoglobin protein is made up of four parts, and therefore called a tetramer. Each
part of the tetramer has the ability to bind an oxygen molecule and carry it from the lungs to the
tissues in where oxygen is needed. When the defective hemoglobin in sickle cell anemia is
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present, it’s referred to as HbS and does not have an oxygen molecule bound to it, unlike the
normal Hb that can combine with O2 it form oxyhemoglobin (HbO2). The HbS tends to form a
precipitate made up of lots of hemoglobin proteins stuck to each other. This precipitate is what
causes the red blood cells to become sickle-shaped.
Question:
How many if the first 6 amino acids in the normal beta chain subunit are essential? = ______.
Peptide Bonds
From all of the unique side groups (R) of the 20 Amino Acids, all of the polypeptides, peptides
and proteins are made. Amino acid chains are linked by covalent peptide bonds from
dehydration synthesis (condensation) reactions.
a) Dipeptide = 2 amino acids joined by a peptide bond
b) Tripeptide = 3 amino acids joined by a peptide bond
c) Polypeptide = more than 10 amino acids joined by a peptide bond
d) Peptide = amino acid chain made of less than 50 amino acids
e) Protein = chain of more than 50 amino acids
Figure 6. This shows two amino acids undergoing a dehydration synthesis (condensation) reaction which
involves the removal of a water (H2O) molecule to make a dipeptide. The covalent peptide bond holds the
dipeptide together. This reaction is called Endergonic, because it requires the input of energy.
Proteins have amino acid sequences and lengths that are all different, and their shapes will
depend on the chemistry of the side groups and how they interact with other portions of the
peptide chain. The way that the string of amino acids are arranged may cause them to coil and
twist the peptide chains that help to provide stability in its shape.
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Exercise: Draw the amino acids 1) glycine and 2) valine side by side below and show how by
removing one water molecule (H2O) you could make a dipeptide.
1)
2)
The Shape of a Protein = the Function of a Protein
The 3D shape of a protein in space has fundamental consequences on its actions, so we need to
understand what the factors are that influence the overall shape of a protein.
Proteins have 4 Levels of Structure
Primary: The linear sequence of amino acids that are linked together by covalent peptide bonds.
Secondary: The geometric folding and twisting of the protein into α-helix or a β-pleated sheet.
Tertiary: Three-dimensional globular shape of the protein in space – caused by R group
interactions.
Quaternary: Two or more polypeptide chains that bond together. Not all proteins will have this
structure.
Figure 7. Shows the four Levels of Structure of Proteins. Not all proteins will have quaternary structures.
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Denaturation of a Protein – Losing its Shape!
Protein denaturation is the uncoiling of protein that changes its ability to function. Typically
proteins can be denatured by heat and acid. After a certain point, denaturation cannot be
reversed.
Figure 8. Comparison between a Normal protein and the same protein that has been Denatured. The
denatured protein will lose most or all of its normal function. Some protein can recover from being
denatured and some cannot, depending on the severity of the stress.
Proteins in the Body
As mentioned several times, proteins are numerous, versatile and unique. The synthesis of a
protein is determined by the genetic information encoded in your DNA. The way that
information about proteins are stored, read and synthesized in the body will be very briefly
explored. Proteins are a very dynamic group of molecules in the body, in that they are constantly
being broken down and synthesized in the body. Researchers measure nitrogen balance to study
synthesis, degradation and excretion of protein. Protein has many important functions in the
body. The study of proteins is called proteomics.
Protein Synthesis is Unique for Each Person: Determined by the Amino Acid Sequence.
Information about how to make the proteins we need is stored in the cell nucleus on your DNA
in the form of genes. Genes are a specific sequence of nucleotides (there are 4: A, C, G and T)
in the DNA molecule that code for a product your body will make, like a protein.
The specific gene on your DNA molecule is the long term record of the information (like a ‘blue
print’) and proteins are made by generating a temporary copy of this gene (like a ‘photo copy’),
called messenger RNA (mRNA).
The instructions on the gene are written and read in codons, which are like a 3 letter word made
out of the nucleotides, each unique three letter word calls for a specific amino acid or signals the
start or end of a protein chain.
This mRNA together with ribosomes and transfer RNA (tRNA) in the cytoplasm, work to
assemble amino acids into peptides and proteins. The tRNA contains anticodons that ‘carry’
specific amino acids with it, bringing in the each new amino acid to add to the growing chain,
connecting each amino acid with a covalent peptide bond to make proteins.
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Figure 9. Inside the cell, protein synthesis is shown, which involves Transcription and Translation.
Transcription is the process of making an RNA copy of a gene sequence, called a messenger
RNA (mRNA). This occurs in the nucleus of the cell.
Translation is the process of translating the sequence of mRNA to a sequence of amino acids
that will result in a protein. This occurs in the cytoplasm of the cell with ribosomes and tRNA.
Basic Steps in Protein Synthesis
1. In the nucleus, DNA unwinds, allowing a ‘complementary’ temporary copy of a gene to
be made messenger RNA (mRNA). This is Transcription!
2. The mRNA moves from the nucleus into the cytoplasm and becomes associated with
ribosomes.
3. Along comes transfer RNA (tRNA), which brings in the specific amino acid called for by
the mRNA codon by matching it to the tRNA anticodon. This is Translation!
4. As translation continues, the incoming amino acids form a growing peptide and protein
chain. This is Elongation!
5. Protein synthesis is terminated by a specific code on the mRNA and the completed
protein is release from the ribosomes into the cytosol. This is Termination!
*Sequencing errors can cause alterations in proteins to be made; an example is sickle-cell
anemia.
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Nutrients and Gene Expression
Cells regulate gene expression - which means they ‘read’ genes such that the product of that gene
is made by the body. Note: The term Epigenetics refers to a nutrient’s ability to activate or
silence genes, i.e., control gene expression, without necessarily interfering with the genetic
sequence. There is the possibility that our genes can also be changed. We have seen a great
example of epigenetics in terms of the effect of diet in the Agouti mice study.
The Various Roles of Protein
With the many a varied roles of proteins in the human body, it is worth taking a quick look at an
overview of the roles of proteins in the body as at this time. When it comes to discussing types,
sources and amounts of proteins in a healthy diet, we will have a better idea where and what this
protein is used for. It will also be important to consider the utilization of proteins as fuel when
our bodies are low on glucose stores.
1. Fibrous Proteins create structural matrix for Growth and Maintenance
a) Makes the protein collagen (the most abundant fiber in the human body) as a
component of the matrix filled with minerals to provide strength to bones and teeth.
b) Replaces tissues including the skin, hair, nails and GI tract lining.
2. Enzymes are biological catalysts (they speed up the rate of a chemical reaction in the body
without being consumed). In this way, proteins facilitate anabolic and catabolic chemical
reactions in the body. Many of these chemical reactions are crucial to the digestion of the
ingested nutrients and
3. Hormones regulate many body processes and some hormones are protein. Important examples
are insulin and glucagon, which regulate blood glucose levels.
4. Regulators of Fluid Balance
Proteins that are suspended in the blood are called “Plasma Proteins”. These are critical to
maintaining normal blood volume. The proteins create ‘colloid osmotic pressure’ in the blood.
This force keeps water attracted to return back into to the plasma inside the blood vessel after it
has been forced out of the blood vessel into the interstitium from hydrostatic pressure of the
blood! Proteins also help to maintain the volume of body fluids in the interstitium and in this
way prevent edema - which is excessive tissue fluid accumulating in the tissue spaces. This
impairs gas exchange and tissue health. By helping to maintain the plasma and interstitial fluid
volumes, it helps regulate the composition of body fluids.
5. Acid-Base Regulation occurs by certain proteins in the body.
a) Act as buffers, able to resist changes in pH and therefore help maintain a stable pH.
b) Acids are compounds that release hydrogen ions in a solution
c) Bases are compounds that accept hydrogen ions in a solution
d) Acidosis is high levels of acid in the blood and body fluids
e) Alkalosis is high levels of alkalinity in the blood and body fluids
6. Transporters
a) Carry lipids, vitamins, minerals and oxygen in the throughout the body, in blood and
lymphatic vessels and across cell membranes.
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b) Act as glucose transporters or ion pumps in cell membranes. For example, the Na+/K+
Pump must exist in every living cell in order to continue living and to maintain the
resting membrane potential (RMP) of that cell.
7. Antibodies
a) Fight antigens that invade the body such bacteria and viruses.
b) Provide immunity to fight an antigen more quickly the second time exposure occurs.
8. Source of Energy and glucose if needed – this involves the deamination of amino acids so
that they can be converted to glucose in a process called gluconeogenesis, which means making
glucose from non-carbohydrate sources. Protein can be used for energy if needed; its excesses
are stored as fat.
9. Other Roles
a) Blood clotting by converting fibrinogen into fibrin, which forms a solid blood clot.
b) Vision by creating light-sensitive pigments rhodopsin in the retina.
Protein Metabolism
Key Steps in Protein Digestion and Absorption
In the Mouth: Unlike some starches and lipids that can begin some mild chemical digestion in
the mouth, protein digestion does not commence until it reaches the stomach.
The stomach is highly specialized to handle protein digestion. It starts when the chief cells in the
gastric glands of the stomach release the powerful hydrochloric acid (HCl). Once HCl is made
and released in the stomach the pH goes down to about 2, and this highly acidic environment
denatures the protein strands after the bolus enters the stomach. The high level of HCl also
triggers the conversion the digestive enzyme Pepsinogen (inactive form) to Pepsin (active
form), which works on breaking polypeptides into shorter chains (through hydrolysis). The
activation of a protein by cutting it is called “Proteolytic Activation”.
As the chyme in the stomach is moved to the first portion of the small intestine called the
duodenum, the digestion of protein continues because the protein content in the stomach triggers
the release of the hormone cholecystokinin (CCK) from the mucosal epithelium of the
duodenum small intestine and secreted. This causes the release of further digestive enzymes and
bile from the pancreas and gallbladder, respectively.
Cholecystokinin (from Greek chole, "bile"; cysto, "sac"; kinin, "move") is a peptide hormone of
the gastrointestinal system responsible for stimulating the digestion of fat and protein.
Cholecystokinin also acts as a hunger suppressant.
The pancreas is stimulated to secrete proteases*, which continue the breakdown of peptide
bonds into smaller peptide chains and single amino acids in the small intestine.
*Note: Words that end in –ase denote an enzyme in biology.
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Although the 20 amino acids are different chemically and structurally from each other, all of
them are small enough in terms of their molecular weights to be absorbed from the cells of the
small intestine directly into the blood stream. From there they are transported via the hepatic
portal system to the liver.
Amino Acids and Proteins in the Liver
In the liver, amino acids are used to synthesize new proteins or are converted to energy, glucose,
or fat. Some whole proteins are absorbed intact, such as antibodies from breast milk. It appears
that the most common type of novel peptide fragments we might encounter in our diet are
produced by genetically modified (GM) foods. When these novel (meaning not naturally
encountered in our diet) protein fragments are absorbed by the small intestines into the blood
stream of the body, they are viewed as foreign pathogens and this generates an exaggerated
immune response - based on the protective physiological mechanisms of our body. What occurs
is inflammation and aggravation of the body’s defense systems. These are otherwise known as
food allergies.
How Are Amino Acids Metabolized?
Depending on the body’s need for protein, the liver determines the fate of newly absorbed amino
acids. If an individual is not eating sufficient carbohydrates, amino acids can be converted to
glucose through a process called gluconeogenesis.
Gluconeogenesis = making glucose from non-carbohydrate molecules, such as proteins and fats.
Most amino acids travel to the blood for use by cells. The ‘amino acid pool’ in cells supply the
body’s ongoing needs for protein synthesis. The daily wear and tear on the body causes the
breakdown of hundreds of grams of proteins each day. If you are sick, wounded, burned, injured
or have been vigorously active, extra protein may be needed for healing purposes. The amino
acid pool is the newly absorbed amino acids and component parts from degraded or brokendown cellular proteins. This can be used to create proteins on demand.
More than 200 grams of protein are turned over each day. Almost 50 percent of this protein
turnover (the process of degrading and synthesizing of protein) occurs in the intestines and the
liver. The remaining turnover has other uses, such as the replacement of skin cells and red blood
cells or in the synthesis of thyroid hormones and melanin.
Amino Acids Catabolism for Fuel
Amino acids are used for different purposes in our body. Most of the metabolic pool of amino
acids is used as building blocks to make proteins, and a smaller proportion is used to synthesize
specialized nitrogenated molecules as epinephrine and norepinephrine, neurotransmitters and the
precursors of purines and pyrimidines.
Since amino acids cannot be stored in the body for later use, any amino acid not required for
immediate biosynthetic needs is deaminated and the carbon skeleton that remains is used as
metabolic fuel (10-20 % in normal conditions) or converted into fatty acids via acetyl CoA. The
main products of the catabolism of the carbon skeleton of the amino acids are:
Pyruvate, oxalacetate, a-ketoglutarate, succinyl CoA, fumarate, acetyl CoA and acetoacetyl CoA.
When carbohydrates are not available (starvation, fasting), or cannot be used properly, as in
diabetes mellitus, amino acids can become a primary source of energy by oxidation of their
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carbon skeleton, but also by becoming an important source of glucose for those tissues that only
can use this sugar as metabolic fuel.
The formation of glucose from amino acids (gluconeogenesis) in liver and kidney is intensified
during starvation and this process becomes the most important source of glucose for the brain,
RBC’s and other tissues. During a situation of prolonged starvation, this can be viewed as an
“emergency” and amino acids in skeletal muscle proteins can be used as an energy store,
yielding 25,000 kcal.
In terms of the metabolic fate of the carbon skeleton, Amino Acids can be classified as:
Glucogenic: Amino acids whose catabolism yields to the formation of Pyruvate or Krebs Cycle
metabolites, that can be converted in glucose through gluconeogenesis.
e.g., Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glycine, Histidine,
Methionine, Proline, Serine, and Valine.
Ketogenic: Amino acids that yield acetyl CoA or acetoacetyl CoA (e.g. they do not produce
metabolites that can be converted in glucose).
e.g., Lysine and Leucine (exclusively).
Glucogenic and Ketogenic: Amino acids that yield some products that can become glucose and
others that yields acetyl CoA or Acetoacetyl CoA.
e.g., Isoleucine, Phenylalanine, Tryptophan, Tyrosine and Threonine.
Figure 10. The metabolism of amino acids for fuel in the body, showing the glucogenic and ketogenic
pathways that the various amino acids take.
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Deamination removes the Amine group from Amino Acids.
If amino acids are not sufficiently required by the body, the amino group must go through a
process called deamination - where the amine group is removed and converted to ammonia
(NH3). This is then sent to the liver to be converted to the less toxic urea and eventually excreted
in the urine. After the removal of the nitrogen, the remnants of the amino acids can be converted
to glucose, used as energy, or stored as fat.
O
Urease
H2N – C – NH2 + 2H2O + H+
urea
water
hydrogen
ion
2NH4+
ammonium
ion
+
HCO3bicarbonate
ion
Nonessential amino acids are synthesized through the process of transamination; the liver
transfers an amino group to the keto acid, creating a new, nonessential amino acid and a new
keto acid. Proteins can be used for gluconeogenesis; when bodily stores of glycogen are
depleted, the body turns to glucogenic amino acids (amino acids converted to glucose through
gluconeogenesis) to provide a new supply of glucose.
Excess protein cannot be stored per se as protein, it is converted to body fat; after deamination,
extra carbon skeletons from protein are capable of being changed to fatty acids and stored as
triglycerides in adipose tissue.
General Overview of Protein Metabolism
1. Protein turnover is the continual making and breaking down of proteins in the body
The amino acid pool is the supply of amino acids that are available.
a) Amino acids from food are called exogenous.
b) Amino acids from within the body are called endogenous.
2. Nitrogen Balance = Protein utilization in the body.
a) Zero nitrogen balance is nitrogen equilibrium, when input is equal to output.
b) Positive nitrogen balance is when nitrogen consumed is greater than nitrogen excreted.
c) Negative nitrogen balance is when nitrogen excreted is greater than nitrogen consumed.
3. Using Amino Acids to Make Proteins or Nonessential Amino Acids – cells can assemble
amino acids into the protein needed
4. Using Amino Acids to Make Other Compounds
a) Neurotransmitters are made from the amino acid tyrosine.
b) Tyrosine can be made into the melanin pigment or thyroxine.
c) Tryptophan makes niacin and serotonin.
5. Using Amino Acids for Energy and Glucose
a) No readily available storage form of protein
b) Breaks down tissue protein for energy if needed
6. Deamination of Amino Acids
a) Nitrogen containing amino groups are removed.
b) The two products that result from deamination include ammonia and keto acids.
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7. Using Amino Acids to make Proteins or Nonessential Amino Acids (Transamination)
8. Converting Ammonia to Urea. The process of deamination of amino acids generate ammonia,
which is a toxic substance. The liver is the organ of detoxification of the blood! Thus, ammonia
and carbon dioxide (CO2) are converted in the liver into the much less toxic substance urea by
the enzyme urease.
9. Excreting Urea. Urea is released back into the bloodstream where it is filtered out of the
blood in the renal kidneys and excreted in urine. Increased water intake is necessary with a highprotein diet to flush the excess urea from the body.
a) Excess protein is de-aminated and converted into fat.
b) Nitrogen is excreted.
Protein in Foods
Eating foods of high quality protein is the best assurance to get all the essential amino acids.
Complementary proteins can also supply all the essential amino acids. A diet inadequate in any
of the essential amino acids limits protein synthesis. The quality of protein is measured by its
amino acid content, digestibility, and ability to support growth.
Protein Quality
This can depend on the protein digestibility, which depends on protein’s food source: a) animal
proteins are 90-99% absorbed and; b) plant proteins are 70-90% absorbed. Other foods
consumed at the same time can have an impact on the digestibility of the proteins.
Use of Amino Acid in the Body:
a) The Liver can produce nonessential amino acids.
b) Cells must dismantle other nutrient molecules to produce essential amino acids if they
are not provided in the diet. The limiting amino acids are those essential amino acids that
are supplied in less than the amount needed to support protein synthesis.
Reference Protein is the standard to measure other proteins by. This is used in preschool
children, based on the needs for growth and development for this group of developing children.
High-Quality Proteins – are those proteins which contain all the essential amino acids – they
used to be called “Complete” proteins. Animal foods contain all the essential amino acids. Plant
foods are diverse in amino acid content and tend to be missing one or more essential amino
acids. There are also Complementary Protein – this is done by combining plant foods that
together contain all the essential amino acids, a strategy that should be used by vegetarians.
Protein Regulation for Food Labels
1. List protein quantity in grams
2. % Daily Values is not required but reflects quantity and quality of protein used.
Protein-Energy Malnutrition (PEM), also called protein-kcalorie malnutrition (PCM)
1. Classifying PEM.
a) Chronic PEM and acute PEM.
b) Marasmus or Kwashiorkor, or a combination of the two.
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Marasmus
Marasmus is a form of severe malnutrition or impaired absorption of protein, energy,
vitamins and, minerals; characterized by energy deficiency. A child with marasmus looks
emaciated. This develops slowly and involves severe weight loss and muscle wasting.
Body weight is reduced to less than 60% of normal (expected) body weight for the age.
Marasmus occurrence increases prior to age 1 (from infancy to 18 months of age), whereas
kwashiorkor occurrence increases after 18 months.
It can be distinguished from kwashiorkor in that kwashiorkor is protein deficiency with
adequate energy intake whereas marasmus is inadequate energy intake in all forms,
including protein. Protein wasting in kwashiorkor may lead to edema (abnormal tissue swelling).
Hair and skin problems ensue, can also affects the mental capacity, but a good appetite is
possible. The prognosis is better than it is for kwashiorkor but half of severely malnourished
children die due to unavailability of adequate treatment.
The word “marasmus” comes from the Greek μαρασμός marasmos ("decay").
Figure 11. Shows a photo of a typical example of a child suffering from Marasmus – a severe form of
wasting from protein deficiency.
Kwashiorkor
Kwashiorkor - a form of severe protein–energy malnutrition characterized by, irritability,
anorexia, ulcerating dermatoses, edema (ascites) and an enlarged liver with fatty infiltrates. It
develops after weaning from about 18 months to 2 years of age, with a rapid onset. Sufficient
calorie intake, but with insufficient protein consumption, distinguishes it from marasmus.
Kwashiorkor cases occur in areas of famine or poor food supply. Cases in the developed world
are rare. This name was entered the medical community in 1935 by pediatrician Cicely Williams,
derived from the Ga language of coastal Ghana, translated as "the sickness the baby gets when
the new baby comes". This reflects the development of the condition in an older child who has
been weaned from the breast when a younger sibling comes.
Body weight is reduced to less than 60 to 80% of normal weight for the age. Breast milk
contains proteins and amino acids vital to a child's growth. Some muscle wasting and some fat
retention. In at-risk populations, kwashiorkor may develop after a mother weans her child from
breast milk, replacing it with a diet high in carbohydrates, especially sugar, but deficient in
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protein (for example milk formulas). Hair and skin problems ensue, can also affects the mental
capacity with a loss of appetite.
Figure 12. Shows a comparison between two children suffering from Kwashiorkor and Marasmus, The
distended belly caused by edema is a fast way to differentiate the two disorder, though both involve
severe protein deficiency.
Both of these major protein deficiencies disorders, Marasmus and Kwashiorkor involve
malnutrition and infection. Typically they can be easily differentiated on the following basis:
a) Wasting associated Marasmus.
b) Edema associated with of Kwashiorkor.
Infections are mainly thought to be due to the lack of antibodies to fight infections; resulting in:
a) Fever
b) Fluid imbalances and dysentery
c) Anemia
d) Heart failure and possible death
Rehabilitation
With nutrition intervention, recovery is possible, must slowly increase protein content in diet and
the body will be unaccustomed to digesting and utilizing proteins.
How to Get Enough Protein in Your Diet
The best sources of protein are meats, fish, eggs and dairy products. They have all the essential
amino acids that your body needs. When a protein contains all the essential amino acids it is
called a “complete’ protein. There are also some plants that are high in protein, like quinoa,
legumes and nuts. In fact, quinoa is a complete protein.
In terms of health, since proteins can be viewed as a fundamental building block of the body,
having the appropriate amount in your diet is naturally considered crucial to maintaining good
health. If we don’t get enough from the diet, our health and body composition suffers. A basic
nutrition recommend from the DRI (Dietary Reference Intake) for example is 0.36 g/lbs. (or 0.8
g/kg) of body weight. These are made with the assumptions that people are healthy, that the
protein is mixed quality and the body will use protein efficiently.
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The typical amount for DRI is:
 56 g/day for the average sedentary man.
 46 g/day for the average sedentary woman.
You may ask yourself: What scientific research are these recommendations made from? The
answer would be there have not been any defining experiments to demonstrate a specific level
that needs to be consumed each day. If you’re a healthy person trying to stay healthy, then
simply eating quality protein with most of your meals (along with nutritious plant foods) should
bring your intake into an optimal range. The “right” amount of protein for any one individual
depends on many factors, including activity levels, age, muscle mass, physique goals and current
state of health. Therefore, you are going to have to start being the best judge of whether or not
what you are eating and how much of it, is right for you.
What “Grams of Protein” Really Means
A common misunderstanding is to take the grams of a food as equivalent to its protein content,
e.g., an 8 ounce serving of beef weighs 226 grams, but it only contains 61 grams of actual
protein. A large egg weighs 46 grams, but it only contains 6 grams of protein. The grams of the
macronutrient protein, not the grams of a protein containing food like meat or eggs, needs to be
measured.
Protein is not just about quantity. It’s also about quality. At the risk of sounding repetitive,
generally speaking, animal protein provides all the essential amino acids in the right ratio for us
humans to make full use of them. This makes sense, since animal tissues are similar to our own
tissues. If you’re eating animal products (like meat, fish, eggs, or dairy) every day, then you’re
probably already doing pretty well, protein-wise.
If you don’t eat animal foods, then it is a bit more challenging to get all the protein and essential
amino acids that your body needs. Most people probably don’t really need protein supplements,
but they can be useful for athletes and bodybuilders. Protein can help you lose weight (and
prevent you from gaining it in the first place).
Protein can be important when it comes to losing weight. Eating protein can stimulate the body
to burn calories and boost your metabolic rate as well as reducing your appetite. This is well
supported by science. Protein at around 25-30% of calories has been shown to boost metabolism
by up to 80 to 100 calories per day, compared to lower protein diets.
Probably the most important contribution of protein to weight loss is its ability to reduce appetite
and cause a spontaneous reduction in calorie intake. Protein can be more satiating than both fat
and carbs. In a study in obese men, protein at 25% of calories increased feelings of fullness,
reduced the desire for late-night snacking by half and reduced obsessive thoughts about food by
60%. In another study, women who increased protein intake to 30% of calories ended up eating
441 fewer calories per day. They also lost 11 pounds in 12 weeks, just by adding more protein to
their diet.
In one study, just a modest increase in protein from 15% of calories to 18% of calories reduced
the amount of fat people regained after weight loss by 50%. A high protein intake also helps to
build and preserve muscle mass (see below), which burns a small amount of calories around the
clock. By eating more protein, you will make it much easier to stick to whichever weight loss
diet (be it high-carb, low-carb or something in between) you choose to follow. According to
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these studies, a protein intake around 30% of calories may be optimal for weight loss. This
amounts to 150 grams per day for someone on a 2,000 calorie diet. You can calculate it by
multiplying your calorie intake by 0.075.
The Protein Package
Some high-protein foods are healthier than others because of what comes along with the protein:
healthy fats or harmful ones and beneficial fiber It’s this protein package that’s likely to make a
difference for health.
I went to many web sites and from Conventional Dietitians-Nutritionist you get this advice:
For example, a 6-ounce broiled porterhouse steak is a great source of protein—about 40 grams worth
and but it delivers about 12 grams of saturated fat. For someone who eats a 2,000 calorie per day diet,
that’s more than 60 percent of the recommended daily intake for saturated fat. A 6-ounce ham steak
has only about 2.5g of saturated fat, but it’s loaded with sodium—2,000 mg worth, or about 500 mg
more than the daily sodium max. …so try lentils… it has virtually no saturated fat or sodium.
First of all, as we know and I will keep repeating, saturated fat is NOT bad for you. On the
contrary, it is extremely beneficial to human health. And sodium is NOT bad for you. On the
contrary, it is essential for good health. Who decided on the “max” limit anyway? Please note
that meat will not contain just isolated sodium chloride, but all of the trance minerals, unlike the
salt shaker at your favorite restaurant. If the only reason an idiot dietitian can find to advise you
not to eat red meat is the advice above, then they are… idiots! Chances are they have never
examined the extensive literature on the health benefits of various ‘vilified’ foods but are blindly
accepting the unsubstantiated, or even false myths that are replete in most textbooks on the
subject of Nutrition. Lentils are fine, but without any fats or salts they will be a little bland to
many people’s palates; trust me, most will want to add other things to those lentils!
Also note: There are 5 brain nutrients found only in meat, fish and eggs (not plants). They are: 1)
Vitamin B12, 2) Creatine, 3) Vitamin D3, 4) Carnosine and 5) Docosahexaenoic Acid (DHA).
Thus it would appear we were not exactly meant to be herbivores.
More Protein Can Help You Gain Muscle and Strength
Muscle tissues in the body are made largely of protein. The most abundant type of muscle in the
human body is skeletal muscle (~40% of body mass).This is the muscle that is attached to bone
of the skeleton and is for body movement. Cardiac muscle is found in the heart and smooth
muscle is located in organs such as the stomach and intestines, and lines many blood and
lymphatic vessels in the body.
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Figure 12. Examples of the three different types of muscle tissue in the human body: Cardiac (in the
heart); Skeletal (attached to bones); and Smooth (lining internal organs and vessels). Regardless of the
location or function of the various muscle tissue in the body, it is primarily made up of two contractile
proteins called myosin and actin.
Protein and Amino Acids in the Diet and Supplementations
As with most tissues in the body, muscles are dynamic and are constantly being broken down
and rebuilt. To gain muscle, the body must be synthesizing more muscle protein than it is
breaking down. In other words, there needs to be a net positive protein balance (often called
nitrogen balance, because protein is high in nitrogen) in the body. For this reason, people who
want a lot of muscle will need to eat a greater amount of protein (and lifting heavy things would
also increase muscle mass). It is well documented that a higher protein intake helps build muscle
and strength. Also, people who want to hold on to muscle that they’ve already built may need to
increase their protein intake when losing body fat, because a high protein intake can help prevent
the muscle loss that usually occurs when dieting.
When it comes to muscle mass, the studies are usually not looking at % of calories, but daily
grams of protein per unit of body weight (kilograms or pounds). A common recommendation
for gaining muscle is 1 gram of protein per pound of body weight, or 2.2 grams of protein per kg.
Numerous studies have tried to determine the optimal amount of protein for muscle gain and
many of them have reached different conclusions. Some studies show that over 0.8 grams per
pound has no benefit, while others show that intakes slightly higher than 1 gram of protein per
pound is best.
If you’re carrying a lot of body fat, then it is a good idea to use either your lean mass or your
goal weight, instead of total body weight, because it’s mostly your lean mass that determines the
amount of protein you need.
Level of Activity and Age can Alter Protein Needs
Disregarding muscle mass and physique goals, people who are physically active do need more
protein than people who are sedentary.
If you have a physically demanding job, you walk a lot, run, swim or do any sort of exercise,
then you need more protein. Endurance athletes also need quite a bit of protein, about 0.5 to 0.65
g/lbs of bodyweight.
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Elderly people also need significantly more protein, up to 50% higher than the DRI, or about
0.45 to 0.6 g/ lbs. This can help prevent osteoporosis and sarcopenia (reduction in muscle mass),
both significant problems in the elderly. People who are recovering from injuries may also need
more protein.
Does Protein Have any Negative Health Effects?
Protein has been unfairly blamed for a number of health problems. It has been said that a high
protein diet can cause kidney damage and osteoporosis. However, none of this is supported by
science. Although protein restriction is helpful for people with pre-existing kidney problems,
protein has never been shown to cause kidney damage in healthy people. In fact, a higher protein
intake has been shown to lower blood pressure and help fight diabetes, which are two of the main
risk factors for kidney disease.
If protein really does have some detrimental effect on kidney function (which has never been
proven), it is outweighed by the positive effects on these risk factors. Protein has also been
associated with osteoporosis, however the studies actually show that protein can help prevent
osteoporosis. Overall, there is no evidence that a reasonably high protein intake has any adverse
effects in healthy people trying to stay healthy.
Protein and Chronic Diseases: Proteins in food and the environment are responsible for most
food allergies, which are overreactions of the immune system. Beyond that, relatively little
evidence has been gathered regarding the effect of the amount of dietary protein on the
development of chronic diseases in healthy people.
There is little evidence of normal or excess protein consumption causing heart disease, although
it is routinely stated that this is one of the risks of eating protein, especially protein derived from
animal sources, and particularly red meat. However, if we already know that all proteins are
made of amino acids and that is what they body breaks them down into, what would the sources
of these identical molecules matter.
A common claim is that it may not be the high animal protein intake per se, but more so the high
saturated fat intake as a consequence. This is presumably where the suggestion to ‘eat lean
meat’ comes from. At the risk of sounding extremely repetitive, this nefarious link is again a
complete fairy tale. Literally, this premise is invalid, as it is based on the faulty and essentially
discredited studies Dr. Ansel Keys in the late 1950’s. This thoroughly unscientific belief system
that links diets rich in saturated fats to heart disease has been shamelessly promoted for over 50
years, despite the fact that it is simply not true!
Eating burnt meat or burnt anything is not a good
idea, nor is it good for your health! The Browning
Effect is a chemical reaction between amino acids
and reducing sugars that gives browned foods their
desirable flavor. Seared steaks, pan-fried dumplings,
breads, and many other foods make use of the effect.
At higher temperatures, caramelization and
subsequently pyrolysis become more pronounced.
And a carcinogen called acrylamide can be formed.
You do not want to eat known carcinogens, because
they can casue cancer.
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In terms of excess protein consumption, it is possible that Homocysteine levels may increase the
risk for heart disease but that arginine may protect against cardiac risk. Excessive glutamate may
stimulate appetite and act as an excitotoxin to neurons in the brain, although levels found in
normal animal products would not contain abnormally high amounts.
Adult Bone Loss (Osteoporosis) – it may be that high protein intake associated with increased
calcium excretion, but inadequate protein intake is deleterious to bone health.
Kidney Stress: A very high protein intake increases the work of the kidneys, since deamination
releases NH3 which is converted to urea by the liver, filtered by the kidneys and excreted in urine
as a nitrogenous waste product.
The body cannot store protein; therefore, extra protein is converted to fat (see amino acid
metabolism section).
Protein and Amino Acid Supplements
Protein Powders have not been found to improve athletic performance.
a. Whey protein is a waste product of cheese manufacturing.
b. Purified protein preparations increase the work of the kidneys.
Amino Acid Supplements may not beneficial if taken in isolation, without other components.
a. Branched-chain amino acids provide little fuel and may be toxic to the brain in isolation, for
example glutamate and aspartate.
b. Lysine appears safe in certain doses.
c. Tryptophan has been used experimentally for sleep and pain.
The Disorder of Phenylketonuria
Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder caused by the
extremely low levels or absence the enzyme phenylalanine hydroxylase (PAH), which converts
the essential amino acid Phenylalanine (Phe) into Tyrosine (Tyr).
Normally, the PAH enzyme breaks down any excess phenylalanine (from all of its various
sources in the diet) in the body. If you have PKU, however, the phenylalanine cannot be broken
down and the excess can build up in the blood and brain to toxic levels, affecting brain
development and function.
Untreated PKU can lead to intellectual disability, seizures, and other serious medical problems.
The best proven treatment for classical PKU patients is a strict phenylalanine-restricted diet
supplemented by a medical formula containing amino acids and other nutrients
This disorder is rare, but when identified early in life is very easy to treat. People who are
diagnosed early and maintain a strict diet can have a normal life span with normal mental
development, as long as the regulated diet is maintained for life.
Note: The artificial sweetener aspartame can act as poisons for people with phenylketonuria,
one reason being the high levels of phenylalanine liberated from foods that contain aspartame.
It has been shown that ingesting aspartame, especially along with carbohydrates, can lead to
excess levels of phenylalanine in the brain even in persons who do not have PKU. This is not just
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a theory; large amounts of aspartame over a long period of time produce excessive levels of
phenylalanine in the blood in those who do not have PKU
So what exactly is Aspartame anyway?
You may do a little research and find that the artificial sweetener Aspartame (which goes by
brand name of “NutraSweet” or “Equal’) is made up of two amino acids: Phenylalanine (Phe)
and Alanine (Ala). By default, some may want to persuade others that since aspartame is made
by two amino acids that you usually eat anyway, it is therefore perfectly healthy and safe for you
to consume in your food.
Let’s look a little closer! These two amino acids are synthetically bound together (i.e., ‘in a lab’)
by creating weak methyl ester bonds between Phenylalanine and Alanine. When aspartame is
heated above 86oF (30oC), this weak ester bond break and liberates free methanol. Methanol
(wood alcohol) is a deadly poison. What is body temperature, by the way? It’s about 98.6 oF
(36.8oC), this means that your body heat is enough to generate methanol from whatever food
item aspartame may be added to, especially your favorite diet soda. This can also occur when the
product containing aspartame is stored above this temperature or heated (e.g. “foods" like Jello).
As discussed in class, once in our bodies, methanol gets converted by alcohol dehydrogenase to
formaldehyde – found in embalming fluid, it is a deadly neurotoxin. The recommend
Environmental Protection Agency (EPA) limit is 7.8mg/day A one-liter aspartame-sweetened
beverage contains about 56mg.
Symptoms from methanol poisoning include serious vision problems, headaches, ear buzzing,
dizziness, nausea, gastrointestinal disturbances, weakness, vertigo, chills, memory lapses,
numbness and shooting pains in the extremities, behavioral disturbances, and neuritis.
Formaldehyde is a known carcinogen, causes retinal damage, interferes with DNA replication
and causes birth defects.
The story of Aspartame does not stop at Methanol and Formaldehyde!
Aspartic Acid
Dr. Russell L. Blaylock, Neurosurgeon at the Medical University of Mississippi, has published a
book detailing the damage caused by the excessive ingestion of aspartic acid from aspartame.
Citing almost 500 scientific references, he shows how excess free excitatory amino acids such
as aspartic acid and glutamic acid (= 99% monosodium glutamate or MSG) in our food supply
are causing serious chronic neurological disorders and a myriad of other acute symptoms.
How Aspartate (and Glutamate) Cause Damage
As we know, Aspartate and glutamate are amino acids and they also act as neurotransmitters in
the brain. They are both ‘excitatory’ neurotransmitters that trigger other neurons into action.
Thus, too much aspartate or glutamate in the brain kills certain neurons by allowing too much
calcium influx. It triggers excessive free radicals, which kill the cells. This neural damage is
referred to as "excitotoxins because they over "excite" or stimulate the neural cells to death.
Shortly after ingesting aspartame or products with free glutamic acid (glutamate precursor), the
excess aspartate and glutamate in the blood plasma leads to a high level of those
neurotransmitters in certain areas of the brain – The protective blood brain barrier (BBB)
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normally shields the brain from toxins such as excess glutamate and aspartate, however: 1) it’s
not fully developed children; 2) the hypothalamus is not fully protected by it; 3) it can be
damaged by chronic and acute conditions; and 4) allows seepage of excess glutamate and
aspartate into the brain even when intact.
The excess glutamate and aspartate slowly begin to destroy neurons. The large majority (at least
75 %) of neural cells in a particular area of the brain are killed before any clinical symptoms of a
chronic illness are noticed. A few of the many chronic illnesses that have been shown to be
contributed to by long-term exposure to excitatory amino acid damage include:
Multiple Sclerosis (MS)
Hypoglycemia
Memory loss
Epilepsy
Alzheimer's disease
Amyotrophic Lateral Sclerosis (ALS)
Parkinson's disease
Hormonal problems
Dementia/Brain lesions
Neuroendocrine disorders
It may be that excessive buildup of phenylalanine in the brain can cause schizophrenia or make
one more susceptible to seizures. Therefore, long-term, excessive use of aspartame may provide
a boost to sales of serotonin reuptake inhibitors such as Prozac and drugs to control
schizophrenia and seizures. A good solution to any of these possible health problems is to stop
ingesting toxins and replace them in your diet with organic whole foods. This way you won’t
have to be on any medications and will feel healthy, vibrant and alive.